Assessments On The Efficacy And Safety Of Bevacizumab Combined With Chemotherapy In Patients With Chemotherapy-refractory Advanced Non-squamous NSCLC

Objective To evaluate the efficacy and safety of bevacizumab combined with chemotherapy in advanced non-squamous non-small-cell lung cancer(NSCLC)and explore the dominant population of bevacizumab in the treatment of NSCLC.Methods Retrospective analysis of 40 cases of stage Ⅳ non-squamous NSCLC,for whom one or more prior lines of chemotherapy had failed,and treated with the bevacizumab combined with chemotherapy.Tumor assessments were performed at baseline,after cycles two,and every 8 weeks thereafter until disease progression,which was based on computed tomography and/or magnetic resonance imaging evaluation as defined by RECIST(version 1.1).Adverse events(classified and graded using Common Terminology Criteria for Adverse Events [version 4.0])were also assessed at ba seline until at least 28 days after the last dose of study drug was administered.The relationship between the clinicopathologic features with clinical efficacy was analyzed;Survival curves for PFS were estimated using the Kaplan-Meier and Log-rank test.Results A total of 40 patients were enrolled in the study.21 males and 19 females,median age was 69 years old.35 cases of adenocarcinoma,2 cases of large cell carcinoma and 3 cases of undifferentiated carcinoma.Tumor assessments were performed after 2 cycles treatment: CR was 0(0%),PR was 13(32.5%),SD was 19(47.5%),PD was 8(20.0%),the total ORR was 32.5%,and the disease control rate(DCR)was 80.0%,t he median PFS was 4.5 months(95% CI: 2.8-6.5 months).Grade Ⅲ toxicity including neutropenia(17.5%),gastrointestinal reaction(5.0%),anemia(5.0%),hypertension(5.0%)and thrombocytopenia(2.5%).Grade IV leukopenia occurred in 4 patients,the other toxicity were grade I-II reaction.Sex,age,ECOG PS score,pathological type,differentiation degree,whether distant metastasis,smoking history,chemotherapy lines were no significant associations with ORR and DCR(P>0.05);The ORR and DCR between different EGFR status were significant difference(P<0.05);Sex,age,tumor differentiation degree,changes of tumor markers,whether distant metastasis,smoking history and chemotherapy lines were not associations with PFS(P>0.05);The PFS between different group of ECOG PS score,pathological type,EGFR status and changes of tumor markers were significant difference(P<0.05);The patients of low PS score group has favorable prognosis compared with high PS score group(P<0.05);The patients of adenocarcinoma group has favorable PFS compard with big cell cancer and undifferentiated carcinoma group(P<0.05).The median PFS of EGFR mutation group and without EGFR mutation were 6.50 and 3.50 months,respectively(P<0.05).Compared with the tumor markers not decreased group,the tumor markers decreased group had better DCR and PFS(P<0.05).Conclusions These data show that bevacizumab combined with standard chemotherapy treatment significantly improved PFS with an acceptable safety profile in patients with advanced non-squamous NSCLC refractory to one or more lines of prior chemotherapy.Adenocarcinoma,good performance status,EGFR mutation and decrease of tumor markers after treatment may benefit better and could be regarded as good prognostic factor.A multicenter collaborative study with a large cohort would be required to substantiate the result.